A "hot flush" is a sudden transient sensation ranging from warmth to intense heat and typically accompanied by flushing and perspiration. It is the classic sign of the menopause and the predominant complaint of menopausal women. A positive correlation between plasma levels of calcitonin gene-related peptide (CGRP) and frequency of hot flushes in women has recently been reported (Chen et al., 1993, Lancet (342) 49), in accordance with the potent vasodilatory effect of CGRP (Brain et al., 1985, Nature, (313) 54-56). Also, a positive correlation between CGRP antagonists and diabetes, septic shock and inflammation has been described (Feurstein, G, Willette, R and Aiyar, N., 1995, Can. J. Physiol. Pharmacol. 73:1070-1074).
Recently, a novel heptadecapeptide, nociceptin, was discovered (Meunier et al., 1995, Nature (377) 532-535, Reinscheid et al., 1995, Science (270) 792-794). Nociceptin and analogues thereof have been disclosed in WO 97/07212, EP 813065 and in WO 97/07208. These peptides and inhibitors thereof are said to be useful for antagonizing physiologic effects of an opioid in an animal, and for treating/preventing a disease related to: hyperalgesia, neuroendocrine secretion, stress, locomotor activity, anxiety etc. Jenck, F et. al. also found, that Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress (PNAS Vol. 94,1997). It is well known that triaza-spiro compounds are vasodilating agents and morphine-like analgesics as disclosed in U.S. Pat. Nos. 3,238,216 and 3,155,670 by Janssen.